Project Abstract One in five women in the US are obese (body mass index (BMI) > 30 kg/m2) during pregnancy. The offspring of obese women are at higher risk of cardiovascular disease, diabetes and obesity in later life. These babies often have a higher fat mass at birth and differences in placental nutrient handling which may contribute to these poor long-term outcomes. However, not all obese women have obese babies and it is unknown what specific maternal and placental factors contribute to fat deposition in babies. We have found that obese women metabolize lipids differently in early pregnancy, a time when the developing placenta is exquisitely sensitive to the maternal environment. The developing baby depends upon the placenta for its lipid supply, and later in pregnancy, placentas of obese women handle fats differently than those of lean women, suggesting that lipid delivery to the baby may be altered. The overall goal of this study is to determine how maternal fat metabolism in early pregnancy programs placental lipid metabolism and a baby's fat deposition. We hypothesize that obese women who have a high fat metabolism in early pregnancy will have a unique lipid profile and these lipids will act as ?signals? to the developing placenta, programming placental lipid metabolism in early pregnancy and increasing lipid delivery to the baby and fat accrual. To test this hypothesis, we will recruit two cohorts of women. The first cohort will be lean and obese women that we follow throughout pregnancy, measuring their fat metabolism, diet and body composition in early and again in late pregnancy. We will then measure placental lipid metabolism and their babies' fat mass at birth. In a second cohort of lean and obese women we will measure placental lipid metabolism in early pregnancy. In both cohorts, we will measure specific maternal lipids that are associated with fat metabolism and test the effect of these lipids on placental lipid metabolism pathways. Placental metabolism will be quantified through innovative methods using isotope-labeled tracers to identify specific metabolic pathways affected by maternal lipid signals. Upon completion of the proposed studies we will have determined: 1) which maternal lipids are associated with fat oxidation in lean and obese women in early pregnancy; 2) the effect of maternal lipids on placental fatty acid metabolism in early pregnancy; 3) mechanisms underlying the effect of maternal lipids on placental metabolic pathways and neonatal body composition at term. These studies have the potential to pave the way for nutritional interventions designed to improve the health of future generations.